Obesity is a heterogeneous condition comprising a continuum of phenotypes with various metabolic and inflammatory profiles. Metabolically healthy obesity (MHO) identifies individuals with obesity but a relatively preserved metabolic state, although little is known about the gut microbiome features underlying this phenotype. Here, we analyzed gut microbial network structures of 931 individuals living with metabolically healthy non-obesity (MHNO), MHO, metabolically unhealthy non-obesity (MUNO), and metabolically unhealthy obesity (MUO), performing cross-sectional analyses on feces shotgun metagenomics data. Individuals with MHNO and MHO harbor more robust and functionally cohesive microbial networks, while communities from MUO and MUNO phenotypes exhibit a potentially dysbiotic state with reduced connectivity. A nutritional intervention cohort showed an improvement in network connectivity in parallel with metabolic improvements. Our findings show differences in microbial connectivity and association patterns across metabolic and obesity phenotypes, shedding light on how distinct microbial network structures may associate with host metabolic health and disease.
Background:Systemic lupus erythematosus (SLE) is an autoimmune disease marked by chronic inflammation and frequent metabolic disturbances. Understanding the influence of body weight and hydroxychloroquine on adipokines and inflammatory markers may clarify their role in SLE progression. Purpose:This study examined metabolic health, adipose tissue gene expression, and serum adipokine and inflammatory profiles in normal-weight (NW) and excess body weight (EBW) female patients with SLE and explored associations with disease activity and hydroxychloroquine (HCQ) use. Patients and methods:Fifty women with SLE were classified as NW or EBW. Laboratory analyses included antibodies against double-stranded DNA, complement components (C3, C4), fasting glucose, triglycerides, total and fractionated cholesterol, and C-reactive protein (CRP). Subcutaneous adipose tissue gene expression was assessed by real-time PCR. Results:Mean age, disease duration, and SLEDAI-2K scores were similar between groups (p > 0.05). HCQ dose adjusted by body weight was lower in EBW patients (p < 0.05). EBW patients had higher total cholesterol, LDL-c, CRP, and leptin, with lower adiponectin and reduced adiponectin/leptin ratio (p < 0.05). Adipose tissue expression of TNF-α, LEP, IL-6, and ADIPOQ was elevated in EBW (p < 0.05). Stratifying by adipo/lep ratio (≤5 vs >5) showed similar disease activity (p > 0.05), though patients with preserved adipose function (ratio >5) had higher serum C4 (p = 0.004) and a trend for increased C3 (p = 0.055). Multiple regression indicated HCQ dose (mg/kg/day) was inversely associated with abdominal circumference (β = -0.43; p = 0.003) and fat mass(β = -0.38; p = 0.009) and positively associated with adiponectin (β = 0.45; p = 0.002) and adipo/lep ratio (β = 0.39; p = 0.009). Higher HCQ doses tended to increase HDL-C (p = 0.059) and reduce leptin (p = 0.058). Conclusion:Excess body weight in SLE is linked to an adverse adipokine profile and increased inflammation, raising metabolic and cardiovascular risk. Weight-adjusted HCQ shows protective effects on adipose metabolism, HDL-c, and adiponectin. These findings emphasize individualized, weight-based HCQ therapy and early adipose biomarker assessment to guide precision medicine in SLE management.
Spermidine administration ameliorates hepatic steatosis and cardiometabolic dysfunction in animal models. However, evidence in humans remains limited. We aimed to explore the 1-year longitudinal associations between changes in dietary spermidine intake and changes in hepatic function indexes and cardiometabolic traits in overweight and obese older adults with metabolic syndrome. We used baseline and 1-year follow-up data from 2664 participants from the PREDIMED-Plus trial. Dietary spermidine intake was estimated using a semi-quantitative food frequency questionnaire. Time series clustering identified temporal patterns of 1-year change in spermidine intake. Linear mixed-effects models assessed the associations between spermidine intake clusters and changes in hepatic and cardiometabolic markers. Three distinct spermidine intake patterns were identified across baseline, six months and 1 year follow-up. Cluster 3, characterized by the highest baseline and increased 1-year spermidine intake, was associated with mean reductions in fatty liver index (− 8.97 [− 9.96 to − 7.97], p-int < 0.001), hepatic steatosis index (− 1.88 [− 2.13 to − 1.63], p-int < 0.001), alanine aminotransferase (− 2.93 [− 3.83 to − 2.02] U/L, p-int < 0.05), aspartate aminotransferase (− 1.11 [− 1.76 to − 0.45] U/L, p-int < 0.05) and glycated hemoglobin levels (− 0.14 [− 0.18 to − 0.10]
Introduction/Objective Women with systemic lupus erythematosus (SLE) exhibit increased cardiovascular risk, partly explained by adverse fat distribution. This multicenter cross-sectional study investigated whether fat-free mass (FFM) is independently related to lipid metabolism and cardiovascular risk and identified metabolic clusters combining body composition and lipid parameters in women with SLE from an Ibero-American cohort. Methods and Procedures In this cross-sectional study, clinical, biochemical, anthropometric, and body composition data from 285 adult women with SLE from Brazil, Mexico, and Spain were analyzed. Multivariable linear regression models examined associations between FFM (%) and lipid parameters and cardiovascular risk indices. Model 1 was adjusted for age and center; Model 2 additionally for disease activity and duration; and Model 3 further for hydroxychloroquine dose. Results Higher FFM was independently associated with a more favorable lipid profile. In the fully adjusted model, FFM was inversely associated with LDL-C (p = 0.032), Castelli I (p = 0.032), Castelli II (p = 0.026), and LAP (p < 0.001), and positively associated with HDL-C (p = 0.048). Associations with triglycerides observed in partially adjusted models were attenuated after full adjustment. Conclusions In women with SLE, greater fat-free mass was associated with a more favorable lipid profile and selected atherogenic indices, independent of demographic and disease-related factors. Although causality cannot be inferred due to the cross-sectional design, these findings suggest that lean mass may represent an important component of cardiometabolic health in SLE.
The introduction of incretin-based obesity management medications has transformed the treatment landscape of obesity, enabling significant levels of weight loss. However, substantial interindividual variability in therapeutic response and the high prevalence of weight regain following treatment discontinuation remain major clinical challenges. These limitations highlight the need for strategies that extend beyond pharmacotherapy alone. This conceptual review synthesizes current evidence on glucagon-like peptide-1 (GLP-1) receptor agonists and dual or triple incretin-based therapies, emphasizing the biological factors that modulate treatment efficacy, including host genetics, gut microbiota composition, and metabolic phenotype. Emerging data suggests that genetic variants affecting incretin signaling pathways, as well as microbiome-driven modulation of hormone secretion and energy metabolism, may partially explain heterogeneity in clinical outcomes. Importantly, incretin-based therapies are frequently accompanied by reductions in lean body mass, nutritional inadequacies, and gastrointestinal adverse effects, which may compromise long-term metabolic health and treatment adherence. In this context, precision nutrition approaches integrating nutrigenomics, metabolomics, and microbiome profiling offer a complementary framework to personalize dietary strategies, preserve lean mass, mitigate adverse effects, and enhance weight-loss maintenance.By integrating pharmacotherapy with individualized nutritional and lifestyle interventions, obesity management may shift toward more sustainable, biologically informed treatment models that address the chronic and relapsing nature of obesity.
